A Clinical Trial to Assess the Safety of Oral SRT2104 and Its Effects on Vascular Dysfunction in Otherwise Healthy Cigarette Smokers and Subjects With Type 2 Diabetes Mellitus

The primary purpose of this study is to evaluate the safety and tolerability of SRT2104 (2.0 g administered once daily for 28 days) and to examine the effects of SRT2104 (2.0 g administered once daily for 28 days) on reversing vasomotor and fibrinolytic dysfunction in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state. This study will investigate the effects of SRT2104 on the reduction of platelet activation markers (platelet-monocyte aggregates), and to evaluate the effects of SRT2104 on platelet and monocyte surface markers (P-selectin, CD11b), inflammatory markers (high sensitivity CRP, IL-6, SAA, TNF-α and sCD40L), and markers of oxidative stress (urinary and plasma F2-isoprostanes and nitrotyrosine). Further goals of this study is to characterize the pharmacokinetic profile of SRT2104 after a single dose and multiple administrations in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state, and to explore the effects of SRT2104 on potential biomarkers of activity for glucose control (HbA1c, glycated albumin and fructosamine) and/or Sirt1 activation.